Inal Ahmet, Büyükşekerci Murat, Ulusoy Hasan Basri
Department of Pharmacology, Erciyes University School of Medicine, Kayseri, Turkey.
Department of Drug and Pharmaceuticals, Ankara Health Directorate, Ankara, Turkey.
Noro Psikiyatr Ars. 2016 Mar;53(1):12-16. doi: 10.5152/npa.2015.8791. Epub 2016 Mar 1.
To evaluate the antinociceptive effect of mirtazapine and the mechanisms mediating this effect in neuropathic pain in rats with diabetes.
The experiments were performed in Sprague Dawley rats using a hot-plate device. Streptozotocin (STZ) was administered to the rats after taking control measurements. Rats with a blood glucose level of 240 mg/dL or above in the blood specimen obtained from the tail vein 3 days after STZ administration were considered as being diabetic. Three weeks after STZ administration, the hot-plate test was performed. Compared with the control measurements, rats that exhibited >20% decrease in the second hot-plate test measurements were considered to have developed neuropathy. Drugs [mirtazapine, naloxone (opioidergic antagonist), metergoline (serotonergic antagonist), and BRL44408 (adrenergic antagonist)] and drug combinations were administered to those rats that developed neuropathy. After administrating the drugs or drug combinations, the third hot-plate test was performed.
Mirtazapine at doses of 10 and 15 mg/kg exhibited a significant antinociceptive effect. Naloxone, metergoline, or BRL44408 alone did not cause an antinociceptive effect. However, combinations of these drugs with mirtazapine (15 mg/kg) significantly decreased the antinociceptive effect of mirtazapine.
It is suggested that mirtazapine has a significant antinociceptive effect in diabetic neuropathy and that opioidergic, serotonergic, and adrenergic systems have roles to play in this effect.
评估米氮平的抗伤害感受作用及其在糖尿病大鼠神经性疼痛中介导该作用的机制。
实验在斯普拉格-道利大鼠身上使用热板装置进行。在进行对照测量后给大鼠注射链脲佐菌素（STZ）。在STZ注射3天后从尾静脉采集的血样中血糖水平达到或高于240mg/dL的大鼠被视为糖尿病大鼠。STZ注射3周后进行热板试验。与对照测量相比，在第二次热板试验测量中表现出降低超过20%的大鼠被认为已发生神经病变。将药物[米氮平、纳洛酮（阿片能拮抗剂）、美替拉酮（5-羟色胺能拮抗剂）和BRL44408（肾上腺素能拮抗剂）]及药物组合给予那些发生神经病变的大鼠。给予药物或药物组合后，进行第三次热板试验。
10mg/kg和15mg/kg剂量的米氮平表现出显著的抗伤害感受作用。单独使用纳洛酮、美替拉酮或BRL44408未产生抗伤害感受作用。然而，这些药物与米氮平（15mg/kg）的组合显著降低了米氮平的抗伤害感受作用。
提示米氮平在糖尿病性神经病变中具有显著的抗伤害感受作用，且阿片能、5-羟色胺能和肾上腺素能系统在该作用中发挥作用。
